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Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants
This study is ongoing, but not recruiting participants.
First Received: August 8, 2005   Last Updated: February 1, 2010   History of Changes
Sponsor: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00128661
  Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer.

PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.


Condition Intervention Phase
Cervical Cancer
Precancerous Condition
Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Phase III

Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind, Active Control
Official Title: A Double-Blind, Controlled, Randomized, Phase III Study of the Efficacy of an HPV16/18 VLP Vaccine in the Prevention of Advanced Cervical Intraepithelial Neoplasia (CIN2, CIN3, Adenocarcinoma In Situ [AIS] and Invasive Cervical Cancer) Associated With HPV 16 or HPV 18 Cervical Infection in Healthy Young Adult Women in Costa Rica

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Histopathologically confirmed, incident CIN2+ associated with an HPV16 or HPV18 infection [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occurrence and intensity of solicited local adverse events (AE) and occurrence (either onset or aggravation) of solicited general AEs including urticaria within 30 minutes after each vaccination and over all vaccinations [ Designated as safety issue: Yes ]
  • Occurrence and intensity of solicited local AE and solicited general AE between day 3 and 6 after each vaccination and over all vaccinations [ Designated as safety issue: No ]
  • Occurrence of unsolicited AEs and severe AEs at month 0 through month 48 [ Designated as safety issue: No ]
  • Outcome of all pregnancies [ Designated as safety issue: No ]

Estimated Enrollment: 7500
Study Start Date: June 2004
Detailed Description:

OBJECTIVES:

Primary

  • Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18) L1 virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3 cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the corresponding HPV type at months 0 and 6.

Secondary

  • Determine the duration of protection against HPV 16 or HPV 18 cervical infection in participants treated with the HPV 16/18 L1 VLP/AS04 vaccine.
  • Determine the safety of this vaccine in these participants, regardless of their initial HPV 16/18 DNA status.
  • Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared with control in preventing CIN2+ associated with any oncogenic HPV type cervical infection in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6.
  • Compare the efficacy of the candidate vaccine with control in preventing CIN2+ associated with HPV 16 or HPV 18 cervical infection, detected within the lesional component of the cervical tissue specimen by PCR, in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked immunosorbent assay (ELISA) at month 0.
  • Compare the efficacy of the candidate vaccine with control in preventing persistent HPV 16 or HPV 18 cervical infection in these participants.
  • Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4 monoclonal antibody inhibition enzyme immunoassay in the first 600 participants randomized to receive HPV 16/18 L1 VLP/AS04 vaccine.

OUTLINE: This is a randomized, controlled, double-blind, parallel-group study. Participants are randomized to 1 of 2 treatment arms.

  • Arm I: Participants receive human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine intramuscularly (IM) once in months 0, 1, and 6.
  • Arm II: Participants receive hepatitis A vaccine (Havrix®) IM once in months 0, 1, and 6.

After completion of study treatment, participants are followed at 6 months and then at least annually for 3 years.

PROJECTED ACCRUAL: Approximately 7,500 participants will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 25 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

DISEASE CHARACTERISTICS:

  • Healthy participants

    • Deemed to be in good general health by history and physical examination
  • Resident of Guanacaste Province of Costa Rica and surrounding areas

    • Must remain a resident for ≥ 6 months after the first study vaccination

PATIENT CHARACTERISTICS:

Age

  • 18 to 25

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • No history of chronic hepatitis requiring treatment
  • No acute or chronic clinically significant hepatic function abnormality by physical examination or laboratory findings
  • No known history of hepatitis A infection

Renal

  • No history of kidney disease requiring treatment
  • No acute or chronic clinically significant kidney function abnormality by physical examination or laboratory findings

Cardiovascular

  • No acute or chronic clinically significant cardiovascular function abnormality by physical examination or laboratory findings

Pulmonary

  • No acute or chronic clinically significant pulmonary function abnormality by physical examination or laboratory findings

Immunology

  • No history of allergic disease
  • No history of autoimmune disorder requiring treatment
  • No history of allergic reaction (e.g., difficulty breathing) to any vaccine
  • No suspected allergy or reaction likely to be exacerbated by a component of the study vaccines (e.g., 2-phenoxyethanol or neomycin)
  • No hypersensitivity to latex
  • No diagnosis or suspicion of any immunodeficient condition by medical history or physical examination

Other

  • Not pregnant or nursing

    • No delivery within the past 3 months
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 30 days before, during, and for 60 days after completion of study treatment
  • Able to speak or understand Spanish
  • Mentally competent
  • Able to undergo pelvic exam (i.e., no heavy bleeding [menstruation or otherwise] or heavy vaginal discharge)
  • No history of cancer requiring treatment
  • No history of diabetes requiring treatment
  • No history of other chronic conditions requiring treatment
  • No acute or chronic clinically significant neurologic function abnormality by physical examination or laboratory findings
  • No other acute disease
  • No fever ≥ 37.5º C

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 6 months since prior chronic administration (i.e., > 14 days) of immune-modulating drugs
  • More than 90 days since prior immunoglobulins
  • More than 30 days since prior and no other concurrent investigational or non-registered vaccines
  • More than 30 days since prior registered vaccines
  • More than 8 days since prior routine meningococcal, hepatitis B, influenza, or diphtheria/tetanus vaccine
  • No prior vaccination against hepatitis A
  • No prior vaccination against human papillomavirus
  • No prior monophosphoryl lipid A or AS04 adjuvant

Chemotherapy

  • Not specified

Endocrine therapy

  • More than 6 months since prior chronic administration (i.e., > 14 days) of corticosteroids (e.g., ≥ 0.5 mg/kg/day of prednisone or equivalent)
  • Concurrent inhaled or topical steroids allowed

Radiotherapy

  • Not specified

Surgery

  • No prior hysterectomy

Other

  • More than 6 months since prior chronic administration (i.e., > 14 days) of immunosuppressants
  • More than 30 days since prior and no other concurrent investigational or non-registered drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00128661

Locations
Costa Rica
Proyecto Epidemiologico Guanacaste
Liberia, Costa Rica
Sponsors and Collaborators
Investigators
Study Chair: Rolando Herrero, MD Proyecto Epidemiologico Guanacaste
Principal Investigator: Allan Hildesheim, PhD National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000441189, NCI-04-C-N191, NCI-590299/009, GSK-590299/009
Study First Received: August 8, 2005
Last Updated: February 1, 2010
ClinicalTrials.gov Identifier: NCT00128661     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
cervical cancer
cervical intraepithelial neoplasia grade 2
cervical intraepithelial neoplasia grade 3

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Precancerous Conditions
Genital Neoplasms, Female
Uterine Diseases
Urogenital Neoplasms
Cervical Intraepithelial Neoplasia
Carcinoma
Uterine Cervical Neoplasms
Genital Diseases, Female
Neoplasms
Uterine Cervical Diseases
Neoplasms by Site
Carcinoma in Situ
Uterine Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 04, 2010